Public Release Summary - Decoquinate in the product Deccox
xxx|Section Heading|Document Title
Public Release Summary
on the evaluation of the new active Decoquinate in the product
Deccox
APVMA Product Number 54134
( Commonwealth of Australia 2016
This work is copyright. Apart from any use permitted under the
Copyright Act 1968, no part may be reproduced without permission
from the Australian Pesticides & Veterinary Medicines
Authority. Requests and enquiries concerning reproduction and
rights can be made to:
Director Public AffairsAustralian Pesticides and Veterinary
Medicines AuthorityPO Box 6182 KINGSTON ACT 2604Australia
Email: [email protected]
This document is published by the APVMA. In referencing this
document the APVMA should be cited as both author and
publisher.
ISSN: 1443-1335
ISBN: 978-1-925390-20-9
Website: This publication is available from the APVMA website:
www.apvma.gov.au.
Contents
vPreface
vAbout this document
vMaking a submission
viiFurther information
11Introduction
22Chemistry and manufacture
22.1Active constituent properties
22.2Product
32.3Recommendation
43Toxicological assessment
43.1Public health aspects and toxicology summary
53.2Occupational health and safety summary
53.3Evaluation of toxicology
73.4Public health standards
83.5Conclusion
94Residues assessment
94.1Introduction
94.2Metabolism
104.3Analytical methods
104.4Residue definition and marker residue
104.5Residues in chicken tissues
114.6Estimated dietary intake
124.7Recommendations
135Assessment of overseas trade aspects of residues in food
135.1Commodities exported
135.2Destination and value of exports
135.3Comparison of Australian MRLs with overseas MRLs
145.4Potential risk to trade
156Occupational health and safety assessment
156.1Health hazards
156.2Formulation, packaging, transport, storage and
retailing
156.3Use pattern
156.4Exposure during use
166.5Exposure during re-entry
166.6Recommendations for safe use
166.7Conclusion
177Environmental assessment
177.1Introduction
177.2Environmental chemistry and fate
187.3Environmental effects
197.4Prediction of environmental risk
207.5Conclusion
218Efficacy and safety assessment
218.1Evaluation of efficacy data
228.2Evaluation of target animal safety data
228.3Conclusions
239Labelling requirements
25Abbreviations
27Glossary
28References
List of tables
12Table 1: MRLs for animal commodities
14Table 2: International MRLs for decoquinate
Preface
The Australian Pesticides and Veterinary Medicines Authority
(APVMA) is the Australian Government regulator with responsibility
for assessing and approving agricultural and veterinary chemical
products prior to their sale and use in Australia.
In undertaking this task, the APVMA works in close cooperation
with advisory agencies, including the Department of Health and
Ageing, Office of Chemical Safety (OCS), Department of the
Environment (DotE), and State Departments of Primary
Industries.
The APVMA has a policy of encouraging openness and transparency
in its activities and of seeking community involvement in decision
making. Part of that process is the publication of Public Release
Summaries for products containing new active constituents.
The information and technical data required by the APVMA to
assess the safety of new chemical products, and the methods of
assessment, must be consistent with accepted scientific principles
and processes. Details are outlined in the APVMA’s regulatory
guidelines.
This Public Release Summary is intended as a brief overview of
the assessment that has been conducted by the APVMA and the
specialist advice received from its advisory agencies. It has been
deliberately presented in a manner that is likely to be informative
to the widest possible audience thereby encouraging public
comment.
About this document
This is a Public Release Summary.
It indicates that the Australian Pesticides and Veterinary
Medicines Authority (APVMA) is considering an application for
registration of an agricultural or veterinary chemical. It provides
a summary of the APVMA’s assessment, which may include details
of:
· the toxicology of both the active constituent and product
· the residues and trade assessment
· occupational exposure aspects
· environmental fate, toxicity, potential exposure and
hazard
· efficacy and target animal safety.
Comment is sought from interested stakeholders on the
information contained within this document.
Making a submission
In accordance with sections 12 and 13 of the Agvet Code, the
APVMA invites any person to submit a relevant written submission as
to whether the application for registration of should be granted.
Submissions should relate only to matters that the APVMA is
required, by legislation, to take into account in deciding whether
to grant the application. These matters include aspects of public
health, occupational health and safety, chemistry and manufacture,
residues in food, environmental safety, trade, and efficacy and
target crop or animal safety. Submissions should state the grounds
on which they are based. Comments received that address issues
outside the relevant matters cannot be considered by the APVMA.
Submissions must be received by the APVMA by close of business
on 24 February 2016 and be directed to the contact listed below.
All submissions to the APVMA will be acknowledged in writing via
email or by post.
Relevant comments will be taken into account by the APVMA in
deciding whether the product should be registered and in
determining appropriate conditions of registration and product
labelling.
When making a submission please include:
· contact name
· company or group name (if relevant)
· email or postal address (if available)
· the date you made the submission.
All information judged by the APVMA to be confidential
commercial information (CCI) contained in submissions will be
treated confidentially.
Written submissions on the APVMA’s proposal to grant the
application for registration that relate to the grounds for
registration should be addressed in writing to:
Enquiries
Registration Management and Evaluation
Australian Pesticides and Veterinary Medicines Authority
PO Box 6182
Kingston ACT 2604
Phone:(02) 6210 4701
Fax:(02) 6210 4721
Email:[email protected]
Further information
Further information can be obtained via the contact details
provided above.
Further information on public release summaries can be found on
the APVMA website: www.apvma.gov.au.
1 Introduction
The Australian Pesticides and Veterinary Medicines Authority
(APVMA) has before it an application from Zoetis Australia Pty Ltd
for registration of a new product, DECCOX, containing the new
active constituent. decoquinate.
This publication provides a summary of the data reviewed and an
outline of the regulatory considerations for the proposed
registration of DECCOX, and approval of the new active
constituent.
Decoquinate is a chemically synthesized 4-hydroxyquinolone
anti-protozoan agent. DECCOX is a feed additive and an oral powder
that contains 60 g/kg decoquinate. The proposed use is for the
prevention and control of coccidiosis caused by Eimeria tenella, E.
necatrix, E. acervulina, E. mivati, E. maxima and E. brunetti in
broiler chickens.
DECCOX is administered in complete feed at an inclusion of 500 g
of DECCOX in each tonne of feed to provide 30 mg decoquinate per
kilogram. The medicated feed is fed to broiler chickens as the only
source of feed from day old to slaughter.
DECCOX will be packaged in 25 kg containers.
DECCOX is registered in the EU, USA, Japan, New Zealand, China,
Taiwan and Korea.
The APVMA seeks public comment on the product outlined in this
document prior to the product being registered for use in
Australia. The APVMA will consider all responses received during
the public consultation period in deciding whether the product
should be registered and in determining conditions of registration
and product labelling.
2 Chemistry and manufacture
2.1 Active constituent properties
The chemical active constituent decoquinate has the following
properties:
Common Name (ISO):
Decoquinate
Chemical Name:
Ethyl 6-n-decyloxy-7-ethoxy-4-quinoline-3-carboxylate
CHEMICAL NAME (CAS):
3-quinolinecarboxylic acid, 6-(decyloxy)-7-ethoxy-4-hydroxy-,
ethyl ester
Product Name (IUPAC):
DECCOX
CAS Registry Number:
18507-89-6
Empirical Formula:
C24H35NO5
Molecular Weight:
417.54
Physical Form:
Powder
Colour:
Cream
Melting Point:
242-245oC
Structural Formula:
2.2 Product
Dose form: Oral feed additive (premix)
Formulation type: Powder
Level of active: 60 g/kg decoquinate
Physical properties – Appearance: The product is a cream to buff
fine powder
Storage and stability
The applicant provided the results of real time and accelerated
stability testing conducted using samples stored in the proposed
commercial containers. The results indicated that the formulated
product is expected to be stable for the duration of the shelf life
when stored below 25°C (Air Conditioning) in the proposed
commercial packaging.
Packaging
The product will be packaged in 25 kg multi-wall kraft paper bag
with polyethylene liner. Based on the storage stability results,
the product is not expected to have an adverse effect on the
packaging and the packaging is not expected to have an adverse
effect on the product.
2.3 Recommendation
The Chemistry and Manufacturing Section of the APVMA evaluated
the chemistry and manufacturing aspects of the decoquinate. All of
the information (including the physico-chemical properties,
spectral identification, manufacturing and quality control aspects,
impurity formation, active constituent specification, stability,
batch analysis data, analytical methods and packaging information)
necessary for the approval of this new active constituent have been
provided. The Chemistry and Manufacturing Section is satisfied that
the application requirement is met.
3 Toxicological assessment
The Office of Chemical Safety (OCS) within the Department of
Health has conducted the toxicology assessment of decoquinate and
DECCOX.
The toxicological database for decoquinate, which consists
primarily of pre-GLP toxicity studies conducted in rats, mice and
dogs, did not conform to current OECD Test Guidelines. However, the
OCS considered that available data, while of reduced reliability,
were sufficient for regulatory purposes.
In interpreting the data, it should be noted that toxicity tests
generally use doses that are high compared with likely human
exposures. The use of high doses increases the likelihood that
potentially significant toxic effects will be identified.
Findings of adverse effects in any one species do not
necessarily indicate such effects might be generated in humans.
However, from a conservative risk assessment perspective, adverse
findings in animal species are assumed to represent potential
effects in humans, unless convincing evidence of species
specificity is available. Where possible, considerations of the
species specific mechanisms of adverse reactions weigh heavily in
the extrapolation of animal data to likely human hazard. Equally,
consideration of the risks to human health must take into account
the likely human exposure levels compared with those, usually many
times higher, which produce effects in animal studies.
Toxicity tests should also indicate dose levels at which the
specific toxic effects are unlikely to occur. Such dose levels as
the No‑Observable‑Effect‑Level (NOEL) are generally used to develop
acceptable limits for dietary or other intakes (ADI and ARfD) at
which no adverse health effects in humans would be expected.
3.1 Public health aspects and toxicology summary
Decoquinate had low acute oral and inhalational toxicity. Acute
dermal toxicity had not been investigated, but is expected to be
low, as decoquinate is poorly water soluble, and neither skin
irritation nor sensitisation tests showed clinical signs of
toxicity. Decoquinate was not a skin or eye irritant in rabbits.
The maximisation test in guinea pigs was negative for skin
sensitisation.
Decoquinate demonstrated low toxicity following repeat-dosing in
dogs and rats; dogs being more sensitive, based on behavioural
changes. Although a formal carcinogenic study was not conducted,
decoquinate is not carcinogenic. A 2-year study in rats and in dogs
found no evidence of an increased incidence of neoplasia. The
active constituent did not cause any effects on reproductive
parameters in a 3-generation reproduction study in rats. Maternal
effects were not observed in developmental studies in rats at the
highest test dose. That dose caused minor developmental variations,
such as retarded skeletal ossification, in foetal animals.
Decoquinate was not teratogenic in rabbits and was negative in a
range of in vitro mutagenicity/genotoxicity studies. Although one
mouse lymphoma forward mutation assay showed equivocal results, the
weight-of-evidence indicated decoquinate was not genotoxic.
Data was not available on the formulated product. The acute
toxicity of DECCOX was estimated from decoquinate and the
excipients. DECCOX is expected to show low acute toxicity from the
oral, dermal and inhalational routes. The product is not expected
to be a skin irritant or a skin sensitiser. DECCOX contains
ingredients which may cause slight mechanical irritation to the
eye.
3.2 Occupational health and safety summary
Worker exposure to DECCOX during mixing and loading on broiler
farms was performed using the Pesticide Handler Exposure Database
Surrogate Exposure Guide (1998) modelling. The OCS determined the
exposure associated with the handling of DECCOX mixed in feed and
from administering the treated feed to livestock to be minimal. It
is expected that the feed distribution will be largely automated,
such as in feeder systems in commercial broiler sheds. Margin of
Exposure estimates indicated that the risk from repeat exposure is
acceptable. Consequently, specific personal protective equipment
for the acute hazards are not required, but safety directions have
been recommended to protect against the mechanical acute eye
irritation.
As post-application exposure to residues of DECCOX is expected
to be lower than the exposure during mixing and loading, the risk
from re-entry was considered to be minimal. Therefore, a re-entry
or re-handling statement was not required for DECCOX.
3.3 Evaluation of toxicologyChemical class
Decoquinate is a 4-hydroxyquinolone anti-protozoal compound.
Data from clinical studies suggested decoquinate acts by arresting
the development of sporozoites following their penetration of the
gut epithelium. Decoquinate significantly inhibited mitochondrial
respiration and electron transport in Eimeria parasites. However,
the mechanism of toxicity is not known.
Toxicokinetics and metabolism
The toxicokinetics studies provided very limited information on
the absorption, distribution, metabolism or excretion of this
active constituent. Metabolites were found in the tissues of rats
fed decoquinate, with highest levels found in the liver and kidney,
and only a small amount excreted in the urine (12 per cent in males
and 6.4 per cent in females). Most of the recovered radioactivity
was the parent compound; three other components were noted in
tissues, but not characterised. There was insufficient data to
enable a metabolic pathway to be proposed. No dermal absorption
data were available for decoquinate.
Acute toxicity
Decoquinate has low acute oral toxicity in the rat (LD50 >
5000 mg/kg bw, no deaths) and low acute inhalational toxicity in
the rat (4-hr LC50 > 4190 mg/m3, nose-only). Studies on acute
dermal toxicity were not provided. The active constituent is
virtually insoluble in water/aqueous solutions, is a low acute oral
toxicant, and showed no clinical signs of toxicity in skin
irritation and sensitisation studies, apart from localised
irritation upon intra-dermal injection. As TGAC decoquinate was
shown to be of low acute oral toxicity and did not elicit clinical
signs of toxicity in skin irritation/sensitisation studies, it was
inferred that the acute dermal toxicity may be of comparable acute
toxicity, and that the acute dermal hazard associated with TGAC
decoquinate exposure is likely to be low. Decoquinate was not
irritating to the eye or skin of rabbits and was not a skin
sensitiser in guinea pigs.
Acute toxicity studies on DECCOX were not provided. The
potential acute oral, dermal, and inhalational toxicity, and the
eye and skin irritancy and skin sensitisation potential were
extrapolated from toxicity data on the active constituent and the
excipients. Based on the toxicity estimation, the toxicity profile
of DECCOX is similar to decoquinate’s profile. The product is
expected to have low acute oral, dermal and inhalational toxicity.
DECCOX is not expected to be a skin irritant and a skin sensitiser.
It may cause mechanical irritation to the eyes.
Systemic effects
Dogs were more sensitive than rats in short term studies. The
lowest NOEL of 15 mg/kg bw/d was established in a 12-week study
based on subdued behaviour noted at the LOEL of 62.5 mg/kg bw/d.
This behaviour was not reported in the 2-year study in dogs. In an
11-week oral gavage study in rats, decoquinate showed no
treatment-related effects. At high doses (> 120 mg/kg bw/d)
minor changes in body weight and food consumption were recorded in
a 26-week dietary study. Treatment-related systemic toxicity was
not noted in long-term studies in rats administered decoquinate at
the highest test dose of 37.7 and 48.4 mg/kg bw/d for males and
females respectively.
Carcinogenicity
A formal carcinogenicity study was not conducted. The pre-GLP
2-year studies in rat and dog did not show evidence of
carcinogenicity. An in silico report on the structure of
decoquinate suggested that the quinolone component of the structure
is indicative of the potential for carcinogenicity. However, the
report considered the substitution at the 3-position has greatly
reduced this potential. Overall, it was concluded that decoquinate
is not likely to be a carcinogen.
Genotoxicity
Decoquinate was tested in vitro for genotoxicity in several
studies. The weight-of-evidence indicated decoquinate is not
genotoxic. In two GLP, non-Guideline Ames tests, decoquinate was
not mutagenic. However, the studies tested up to the maximum
solubilisation concentration as claimed by the study authors, which
was 5.7 µg/plate in one study and 10 000 μg/plate in the other,
despite using the same solvent (DMSO). Both studies showed no
cytotoxicity and test material precipitation.
Results from a mouse lymphoma forward mutation assay were
equivocal for the groups treated with metabolic activation. The
highest dose of 2.5 mg/mL showed significantly elevated mutant
frequency, but as this group also showed high cytotoxicity, the
group was disregarded. At the next lower dose of 2 mg/mL, the
mutant frequency was almost double that of the vehicle controls and
the mutant frequency showed a rough dose response for those
cultures treated with S9.
Decoquinate did not induce chromosomal aberration in Chinese
Hamster ovary cells in a chromosome aberration assay. Only three
low doses were tested in this study (0, 0.05, 0.15 and 0.25 µg/mL).
They were not sufficient to cause cytotoxicity. In a second
chromosome aberration assay, a wider range of doses were tested
(30, 75.1, 150, 225 and 300 μg/mL). There was no evidence of
chromosomal aberration induction, either with or without metabolic
activation. The period of exposure of the test substance prior to
harvesting was notably different from standard chromosome
aberration assay protocols.
In a published journal article (Ohta et al, 1980) decoquinate
was reported negative (i.e. not mutagenic) in a rec-assay (repair
test) and reverse mutation assay.
Reproductive and developmental toxicity
A 3-generation rat reproductive study showed no effects on
reproductive parameters. The NOEL of 61 / 71 mg/kg bw/d for M/F was
the highest dose tested. Foetal toxicity in the rat developmental
study was noted as developmental variations (retarded ossification)
at the highest test dose of 300 mg/kg bw/d, while at the same high
dose in rabbits there was no evidence of maternal toxicity or a
teratogenic effect. A decrease in the mean live foetuses/litter at
≥100 mg/kg bw/d was not ruled out as unrelated to treatment, due to
deficiencies in the study and specific endpoints not being
reported. The NOEL for foetotoxicity in this study was established
at 60 mg/kg bw/d.
3.4 Public health standardsPoisons scheduling
On the 27 June 2013, the delegate to the Secretary to the
Department of Health and Ageing decided to include decoquinate in
Schedule 5 of the Standard for the Uniform Scheduling of Medicines
and Poisons with no cut-off. The implementation date was 1
September 2013.
NOEL/ADI
The acceptable daily intake (ADI) for humans is the level of
intake of a chemical that can be ingested daily over an entire
lifetime without appreciable risk to health. It is calculated by
dividing the overall NOEL for the most sensitive toxicological
endpoint from a suitable study (typically an animal study) by an
appropriate safety factor. The magnitude of the safety factor is
selected to account for uncertainties in extrapolation of animal
data to humans, intra-species variation, and the completeness of
the toxicological database and the nature of the potential
toxicologically significant effects.
An ADI of 0.007 mg/kg bw/d for decoquinate was established in
1969, but details on its determination were not available. The
available data were examined to revise the ADI.
Long-term studies in rats and dogs with decoquinate did not
establish clear evidence of treatment-related adverse effects.
There were no findings of toxicological significance at the highest
dose tested. Decoquinate appeared to be of low oral toxicity in all
animals tested, with dogs being the most sensitive species.
Therefore, the sub-chronic toxicity study in dog was taken as the
most appropriate study on which to establish an ADI.
In the 12-week study in dog, subdued behaviour was noted at 62.5
mg/kg bw/d, with the NOEL set at 15 mg/kg bw/d. Based on this NOEL
to which a 200-fold safety factor was applied, consisting of
factors of 10 each for intra-species and inter-species variation,
together with an additional factor of 2 for the database consisting
largely of studies conducted prior to GLP and modern standards, the
ADI was revised to 0.075 mg/kg bw/d. A correction for oral
absorption was not considered appropriate because of the limited
metabolism studies available.
ARfD
The acute reference dose (ARfD) is the estimate of the amount of
a substance in food or drinking water, expressed on a milligram per
kilogram body weight basis, that can be ingested over a short
period of time, usually in one meal or during one day, without
appreciable health risk to the consumer on the basis of all known
facts at the time of the evaluation.
An ARfD for decoquinate was not considered necessary. Data from
acute toxicity studies and reproductive/developmental toxicity
studies suggested that the acute effects associated with a single
exposure to decoquinate are unlikely to present an acute hazard to
people.
3.5 Conclusion
The OCS supports the registration of DECCOX, containing 60 g/kg
decoquinate, for the prevention and control of coccidiosis in
broiler chickens.
4 Residues assessment
4.1 Introduction
Decoquinate is a coccidiostat that is not currently approved for
use in Australia. It is proposed that DECCOX be approved for use as
a feed additive product for the prevention and control of
coccidiosis in broiler chickens. Maximum Residue Limits (MRLs) for
decoquinate in edible chicken tissues need to be established to
cover the proposed use pattern of DECCOX.
One critical radio-labelled total tissue residue decline study
was provided, in which chickens were dosed orally with 2 mg
[14C]-decoquinate twice daily for seven consecutive days. The
dosage was equivalent to that associated with the proposed use of
the product. This study was utilised to establish the marker to
total residue ratios, to recommend the Maximum Residue Limits and
to establish an appropriate withholding period.
4.2 Metabolism
Absorption
Decoquinate was absorbed from the gastrointestinal tract of
chickens. Following administration of 14C-decoquinate, plasma
concentrations of 14C-decoquinate plateaued within 42 hours of the
first treatment. The radiolabelled compound then declined rapidly
within 48 hours of the last treatment. Trace amounts remained in
the blood and plasma.
Distribution
At 6 hours after the last dose, the highest total radioactive
residues (TRR) was found in liver (0.444 mg eq/kg) and kidney
(0.411 mg eq/kg). The rank order for total radioactivity in edible
tissues was liver>kidney>>>skin/fat>>muscle. The
major route of elimination when decoquinate was administered orally
to broiler chickens was via excreta.
Metabolism
The data suggested that the metabolism of decoquinate in
chickens is limited. Following administration of 14C-decoquinate,
tissue residues were characterised as mainly parent decoquinate. In
kidney, two major metabolites were found, K1 which accounted for a
maximum of 49 per cent of the TRR and K2 which accounted for a
maximum of 24 per cent of the TRR. Metabolites corresponding to K1
and K2 were also detected in the liver (L1 and L2). Following
derivatisation, metabolites K1/L1 and K2/L2 were tentatively
identified as quinolone and hydroxypyridine derivatives of
decoquinate.
4.3 Analytical methods
Details of two analytical methods for the analysis of
decoquinate in chicken tissue using HPLC were provided. The Limit
of Quantification (LOQ) for all chicken tissues (liver, kidney,
muscle and skin/fat) were reported to be 0.02 mg/kg for one method
and 0.05 mg/kg for the other.
4.4 Residue definition and marker residue
A residue definition for decoquinate as parent decoquinate is
currently established in the MRL standard.
The marker residue (parent decoquinate) to total radioactive
residues ratios at 2 hours after the final treatment were 0.7, 0.5,
1.0 and 0.9 in liver, kidney, muscle and skin/fat, respectively.
The marker residue to total radioactive residues ratios at 6 and 12
hours after the final treatment were quantitatively similar and
were 0.9, 0.4, 1.0 and 0.9 in liver, kidney, muscle and skin/fat,
respectively.
4.5 Residues in chicken tissues
The critical radio-labelled residue study conducted on chickens
involved two daily doses of 14C-decoquinate at 2 mg
decoquinate/dose (equal to 4 mg decoquinate/day). The proposed use
of DECCOX involves a dose concentration of 30 mg decoquinate / kg
complete ration. A model broiler chicken in Australia may consume
0.15 kg feed per day on average and therefore may consume 4.5 mg
decoquinate per day as a result of the proposed use. Decoquinate
residues in chicken liver, kidney, muscle and skin/fat samples were
determined at 2, 6 and 12 hours after the last dose. The highest
residue levels from those sampling times are relevant to the
proposed withholding period of 0 days.
The results of this radio-labelled residue study found the
highest upper one-sided 95 per cent confidence limit of the 95th
percentile (95/95) residue for parent decoquinate (the marker
residue) calculated at each sampling time (2, 6 or 12 hours after
the last dose) to be 0.419, 0.268, 0.239 and 0.069 mg/kg in liver,
skin/fat, kidney and muscle respectively. The estimated 95/95
tolerance limit for parent decoquinate was 0.61 mg/kg in liver,
0.32 mg/kg in kidney, 0.07 mg/kg in muscle and 0.30 mg/kg in fat at
2 hours after the last dose based on the regression analysis. While
the proposed MRLs of 1.0 for liver and skin/fat, 0.8 mg/kg for
kidney and 0.5 mg/kg for meat are higher than the residues observed
in the trial, they are considered appropriate, noting the size of
the dataset available and that they are harmonised with the MRLs
established by EFSA. The MRLs are not expected to result in human
health concerns based on the conservative JECFA diet.
The proposed withholding period for meat of ‘Zero (0) days’ is
supported by the available residue data.
As the proposed use is for broiler chickens and residue data for
eggs are not available the proposed restraint ‘DO NOT USE in laying
hens’ is supported from a residues perspective. The withholding
period (restraint) for eggs of ‘DO NOT USE in chickens which are
producing or may in the future produce eggs or egg products which
may be used or processed for human consumption’ should be
associated with the proposed use.
4.6 Estimated dietary intake
The APVMA utilises the procedure used by JECFA for estimating
MRL values, but retains its internally harmonised approach to
estimating residue intakes for food safety assessment. The dietary
exposure calculation incorporating the JECFA daily food basket
represents <2 per cent of the decoquinate ADI.
The chronic dietary exposure to decoquinate is estimated by the
National Estimated Daily Intake (NEDI) calculation encompassing all
registered/temporary uses of the chemical and the mean daily
dietary consumption data derived primarily from the 1995 National
Nutrition Survey of Australia. The NEDI calculation is made in
accordance with WHO Guidelines and is a conservative estimate of
dietary exposure to chemical residues in food. The NEDI for
decoquinate is equivalent to <1 per cent of the ADI. It is
concluded that the chronic dietary exposure of decoquinate is
acceptable.
The acute dietary exposure is estimated by the National
Estimated Short Term Intake (NESTI) calculation. The NESTI
calculations are made in accordance with the deterministic method
used by the JMPR with 97.5th percentile food consumption data
derived primarily from the 1995 National Nutrition Survey of
Australia. NESTI calculations are conservative estimates of
short-term exposure (24 hour period) to chemical residues in food.
The Office of Chemical Safety has not established an ARfD for
decoquinate and a NESTI calculation is therefore not required.
4.7 Recommendations
The following use pattern is supported from a residues
perspective:
ANIMAL
PURPOSE
DOSE RATE
Broiler chicken
For the prevention and control of coccidiosis
Thoroughly mix 0.5 kg / tonne of complete ration to provide 30
mg decoquinate/kg and feed continuously as the only source of
feed.
Restraints
DO NOT USE in laying hens.
Withholding periods
MEAT: Zero (0) days
EGGS: DO NOT USE in chickens which are producing or may in the
future produce eggs or egg products which may be used or processed
for human consumption.
The following amendments are proposed to the MRL standard:
Table 1: MRLs for animal commodities
Compound
Food
MRL (mg/kg)
ADD:
Decoquinate
Chicken kidney
0.8
Chicken liver
1
Chicken meat
0.5
Chicken skin / fat
1
5 Assessment of overseas trade aspects of residues in food
5.1 Commodities exported
Poultry are currently listed in Part 5B of the APVMA regulatory
guidelines as a major export commodity.
5.2 Destination and value of exports
In 2013-14 Australia produced 1,067 kt of chicken meat but only
exported 38.4 kt (3.6 per cent of production).
Very little Australian chicken meat is exported. Australian
chicken meat is exported primarily to South Africa, the
Philippines, Hong Kong, Singapore and the South Pacific islands.
The bulk of chicken meat exports have been made up of frozen cuts
and edible offal (including any other parts of the chicken that are
suitable for human consumption such as feet, liver, kidneys
etc).
5.3 Comparison of Australian MRLs with overseas MRLs
The Codex Alimentarius Commission (Codex) is responsible for
establishing Codex Maximum Residue Limits. Codex MRL are primarily
intended to facilitate international trade, and accommodate
differences in Good Agricultural Practice employed by various
countries. Some countries may accept Codex CXLs when importing
foods, however decoquinate has not been considered by Codex.
The following relevant international MRLs have been established
for decoquinate and it is noted that the residue definition in each
jurisdiction is parent decoquinate:
Table 2: International MRLs for decoquinate
Commodity
Tolerance for residues arising from the use of decoquinate
(mg/kg)
Australia
(proposed)
EU
USA
Canada
Japan
China
Taiwan
Korea
Chicken kidney
0.8
0.8
2
2
0.1
2
2
-
Chicken liver
1
1
2
2
0.1
2
2
-
Chicken meat
0.5
0.5
1
1
0.1
1
1
2
Chicken skin/fat
1
1
2
2
2
2
2
-
5.4 Potential risk to trade
It is proposed that decoquinate MRLs at 0.5 mg/kg for meat, 0.8
mg/kg for kidney and 1.0 mg/kg for liver and skin/fat be
established, which are the same as those established in Europe and
is lower than that established by the USA, China and Taiwan (1
mg/kg for skeletal muscle and 2 mg/kg for other tissues). Codex has
not established MRLs for decoquinate and the established Japanese
MRLs for chicken kidney, liver and meat (0.1 mg/kg) are lower than
those proposed. As the proposed Australian MRLs are equal to or
lower than those established by the EU, USA, Canada, China and
Taiwan and as the export of chicken meat accounts for <5per cent
of total Australian production, the trade risk associated with the
proposed use of DECCOX is considered to be low.
6 Occupational health and safety assessment
6.1 Health hazards
Decoquinate (CAS: 18507-89-6) is not listed on Safe Work
Australia’s Hazardous Substances Information System Database (SWA,
2013). With the available toxicology information, OCS has
classified decoquinate as a non-hazardous substance according to
the NOHSC Approved Criteria for Classifying Hazardous Substances
(NOHSC, 2004). Thus, human health risk phrases will not be required
for decoquinate.
Based on toxicology information and concentrations of the active
constituent and other excipients in the product, DECCOX is not
classified as a hazardous substance in accordance with NOHSC
Approved Criteria for Classifying Hazardous Substances (NOHSC,
2004).
6.2 Formulation, packaging, transport, storage and retailing
Decoquinate will be manufactured overseas. DECCOX will be
manufactured overseas and imported into Australia as a finished
product in 25 kg kraft paper bags with polypropylene liner.
6.3 Use pattern
DECCOX is a premix in an oral powder formulation. It is intended
for use in feed to prevent and control coccidiosis in broiler
chickens. For broiler chickens, the rate is 0.5 kg DECCOX/tonne of
feed, sufficient to provide a dose equivalent to 30 mg
decoquinate/kg feed. The draft label states that broiler chickens
should be fed continuously as the only source of feed from day old
to slaughter.
6.4 Exposure during use
Workers in feed mills, poultry farmers and their employees will
be the main users of the product. Workers may be exposed when
opening bags of DECCOX, weighing the product, incorporating it into
feed, and transferring and storing the final feed. Workers will be
exposed to the product predominately by skin contact as well as
inhalation and eye contact during the preparation of stock feed.
The product formulation is expected to reduce the amount of dust
produced, and hence the workers’ inhalational and ocular exposure.
Workers dispensing finished feed to livestock will be exposed to
the product diluted at up to 0.055 per cent (0.0033 per cent w/w
active constituent) on a regular basis.
Occupational exposure studies have not been conducted for
decoquinate or DECCOX. In the absence of exposure data for the
proposed mode of application, the Pesticide Handler Exposure
Database (PHED) Surrogate Exposure Guide (1998) was used to
estimate potential worker exposure during mixing and loading. The
exposure associated with handling of mixed product in feed is
expected to be minimal and has not been quantitatively estimated in
this particular case.
The toxic endpoint and NOEL was derived from a repeat dose study
in animals. In this evaluation, a Margin of Exposure (MOE) ≥ 200
was considered acceptable. This MOE took into account both
interspecies extrapolation and intra-species variability and the
quality and completeness of the available data on decoquinate.
DECCOX is expected to be a low acute oral and dermal toxicant.
The product is not expected to be a skin irritant or a skin
sensitiser. Although the formulation is expected to greatly reduce
the amount of dust produced, mechanical ocular irritation is
possible. The risks associated with repeat worker exposure to
DECCOX were considered low. Overall, the OCS determined that no
specific PPE was necessary, though precautionary statements
associated with the potential ocular irritation were considered
appropriate.
6.5 Exposure during re-entry
Workers may be exposed to residues of DECCOX when clearing away
uneaten feed or cleaning equipment. Dermal, inhalational and ocular
exposure to dusts may occur during this activity. However,
considering that dust formation is reduced and the amount of active
constituent in the final feed mix given to broiler chickens is low
(30 mg active constituent/kg of feed), the likely level of exposure
is considered low and expected to be much lower than exposure
during the mixing/loading of the pre-mix product. The risk from
re-entry is minimal when the limited re-handling of treated feed
and the toxicity profile of decoquinate and DECCOX are considered.
Therefore, a re-entry or re-handling statement is not required.
6.6 Recommendations for safe use
Users should follow the First Aid Instruction and Safety
Directions on the product label. The recommended first aid
instruction is, If poison occurs, contact a doctor or Poisons
Information Centre. Phone Australia 13 11 26. The recommended
safety directions are, May irritate the eyes. Avoid contact with
eyes. Wash hands after use.
6.7 Conclusion
The OCS supports the registration of DECCOX for the prevention
and control of coccidiosis in broiler chickens. The OCS concludes
DECCOX can be used safely if handled in accordance with the
instructions on the product label. Additional information is
available on the product Safety Data Sheet.
7 Environmental assessment
7.1 Introduction
DECCOX is proposed to be applied orally in feeds and fed
continuously to chickens at 30 mg ac/kg feed from day old to
slaughter.
7.2 Environmental chemistry and fateAbiotic degradation
Decoquinate contains hydrolysable ester groups, based on its
chemical structure. However, it appears from the metabolism of
decoquinate in target animals, the majority of the compound is
excreted as the unchanged parent compound. This indicates
decoquinate is likely to be stable under environmental conditions
and ester cleavage is slow.
Biodegradation
Aerobic soil metabolism
The route and rate of degradation of [14C] decoquinate in soil
under aerobic condition was investigated in three soil types (sandy
loam, loamy sand and clay loam). Soil samples were fortified to a
concentration of 1.28 mg/kg. The test was performed in the dark at
20°C in a closed system and volatiles were trapped in ethandiol and
ethanolamine. Soil samples were taken over a 120 day period.
Decoquinate and its degradation products were separated by HPLC and
TLC.
In all soil types, the freely extractable radioactivity was low:
<6 per cent in sandy loam, <5 per cent in loamy sand and
<9 per cent in clay loam. Radioactivity was associated mainly
with the parent compound. Extraction into sodium hydroxide ranged
from 36-70 per cent in sandy loam, 47-79 per cent in loamy soil and
24-63 per cent in clay loam with no correlation with time. The
combined extracted residue showed that at the end of the study 14
per cent in clay loam, 19 per cent in sandy loam and 32 per cent in
loamy soil of AR was the parent compound. After 16 (loamy sand and
clay loam) to 32 days (sandy loam) an unknown biodegradation
product formed. It increased to 35 per cent in sandy loam, 38 per
cent in loamy sand and 35 per cent in clay loam after 120 days.
Another unknown biodegradation product was formed up to 5 per cent.
In all soil types mineralisation was low; levels of 14CO2 after 120
days were <2 per cent. Based on the percent parent compound in
the combined extracts, DT50s were estimated to be 96, 140 and 116
days for the three soil types.
Metabolism in animals
A broad range of studies were conducted to evaluate the fate,
absorption, distributions, metabolism, and excretion of decoquinate
in the target species. Studies were based on the active ingredient
either labelled or unlabelled in feed.
In rats receiving [14C]-labelled decoquinate in their diets
daily for 11 days, the metabolic plateau based on tissue
concentrations of total radioactivity was achieved after 3 days.
The major component in each tissue investigated was decoquinate,
accounting for up to 43 per cent of the radioactivity in liver and
kidney, and 65 per cent in the muscle and skin with 3 metabolites
being identified. Male rats excreted 12 per cent of the dose in
urine and females excreted 6 per cent in urine. A plateau level of
excretion was achieved after 2 days.
The pharmacokinetics and metabolism of decoquinate in poultry
was investigated using conventional radiometric methods.
In poultry, decoquinate was eliminated rapidly via excreta (mean
90 per cent) within 48 h of the last dose. Tissue residues were low
in terms of percentage dose, with liver and kidney together
accounted for a mean of 0.12 per cent of the total dose at 24 h
post dose. In colostomised chickens, less than 2 per cent of the
dose was excreted in urine, indicating a low oral bioavailability.
The major component in chicken excreta was confirmed as the parent
test material (94 per cent). It was estimated that only 2.6 per
cent of the decoquinate dose passing through the broiler chicken is
converted or metabolized to non-decoquinate components. The
non-decoquinate components have not been identified but are polar
in nature.
Mobility
Soil adsorption study
The Koc value of decoquinate was determined experimentally using
OECD HPLC methodology. At pH 4.4 and 8.5 decoquinate is determined
to have a log Koc >5.6 (Koc >398,107). Based on McCall’s
Mobility Classifications, decoquinate is considered to be
immobile.
Bioaccumulation in aquatic organisms
Based on the metabolism studies, decoquinate is unlikely to be
absorbed systemically to allow tissue bioaccumulation to occur by
oral administration. Because of the very limited aqueous solubility
of decoquinate, the bioaccumulation of decoquinate in fish and
aquatic organisms was not measured. This indicated that there will
be limited aquatic exposure. Further, the high Koc value indicated
that decoquinate is likely to be adsorbed to the soil/sediments.
Therefore, under the proposed use pattern, there is little
potential for bioaccumulation to occur in aquatic organisms.
7.3 Environmental effectsAquatic organisms
Acute toxicity studies of decoquinate on rainbow trout (96 h
LC50 >0.016 mg ac/L), Daphnia magna (48 hr EC50 >0.034 mg
ac/L), algae (72 hr ErC50 >0.073 mg ac/L) indicated that
decoquinate is not toxic to these species up to its limit of water
solubility. At the concentration of 16.3 mg decoquinate/kg dry
weight, no effect on survival and development of sediment dwelling
larvae of the midge Chironomous riparius was observed.
Non-target invertebrates (terrestrial)
Earthworms
The acute toxicity of 14 days LC50 >1000 mg ac/kg soil and
the chronic toxicity of 56 days NOEC = 1000 mg ac/kg based on
reproduction indicated that decoquinate is very slightly toxic to
earthworms, acutely and chronically.
Soil microorganisms
Decoquinate did not have a significant effect on soil
microflora, based on respiration and nitrification at
concentrations of up to 9.2 mg ac/kg dry soil. It was concluded
that decoquinate does not have a long term influence on soil
microbial processes.
Phytotoxicity
Decoquinate did not show any effects on the emergence and growth
of seedlings of wheat (Triticum aestivum), mustard (Brassica alba)
and mung bean (Phaseolus aureus) at concentrations up to 100 mg/kg
dry soil. The LC50 for emergence and EC50 for growth were
determined to be >100 mg/kg dry soil for each of the species
tested. The NOEC was determined to be 100 mg ac/kg soil based on
emergence and growth.
7.4 Prediction of environmental riskBirds
Exposure of birds to decoquinate will be very low, as few
species would frequent cultivated areas where manure will be
applied.
Aquatic organisms
DotE’s environmental risk calculations in the aquatic
compartment were based on a worst case pasture scenario with direct
excretion into surface water by grazing sheep and cattle, and a
worst case run-off in a feedlot situation under Australian farm
practices for cattle. As decoquinate is not toxic to aquatic
organisms up to its limit of water solubility in the submitted
ecotoxicity studies, DotE considered it was not meaningful to
calculate a PNEC, nor a risk quotient RQ = PECsurface water /PNEC.
It was concluded that runoff in the feedlot scenario and treated
cropland as a result of rainfall event from the use of the proposed
product poultry is unlikely to pose an unacceptable risk to the
aquatic compartment.
Non-target invertebrates
The proposed use of DECCOX under Australian farm practices is
not expected to present unacceptable risks to earthworms. This is
based on studies showing that the calculated PECsoil was well below
the toxicological end point tested for earthworms.
Soil micro-organisms
Decoquinate did not have a significant effect on soil microflora
at a concentration of up to 9.2 mg ac/kg dry soil. Based on the
worst case soil concentration of 869 µg/kg soil in a poultry shed
scenario, the calculated risk quotient indicated that there is
unlikely to be an unacceptable risk to soil micro-organisms.
Non-target vegetation
Based on the worst case soil concentration of 869 µg/kg soil in
a poultry shed scenario and the EC50 of >100 mg ac/kg dry soil,
the risk quotient indicated an acceptable risk to non-target
vegetation.
7.5 Conclusion
DotE recommended that the APVMA be satisfied that the proposed
use of DECCOX on poultry would not be likely to have an unintended
effect that is harmful to animals, plants or things, or to the
environment under Section 14 subsection 1 of the Agvet Codes.
In order to be satisfied that the proposed uses of the product
will not lead to an unintended effect that is harmful to animals,
plants or things, or to the environment at the proposed rate and
following good agricultural practice, DotE recommended the
following amendments to the label particulars:
Protection of Wildlife, Fish and Crustaceans and the
Environment
DO NOT contaminate wetlands or watercourses with this product or
used containers.
Disposal
Shake and empty contents into medicated feed. Do not dispose of
undiluted chemicals on-site. If not recycling, break, crush or
puncture and deliver empty packaging to an approved waste
management facility. Empty bag and left-over product should not be
burnt.
8 Efficacy and safety assessment
Decoquinate is not approved currently for use in a veterinary
chemical product. It is an antiprotozoal agent. The product,
DECCOX, contains 60 g/kg decoquinate and claims to be effective in
preventing and controlling coccidiosis caused by Eimeria tenella,
E. necatrix, E. acervulina, E. mivati, E. maxima and E. brunetti in
broiler chickens. The label instructs the mixing of 500 g DECCOX in
each tonne of complete feed to provide 30 mg decoquinate/kg feed
(30 ppm) and feeding the medicated feed to broiler chickens
continuously as the only source of feed from day old to slaughter.
The product is prohibited from administration to chickens which are
producing or may in the future produce eggs or egg products which
may be used or processed for human consumption.
8.1 Evaluation of efficacy data
The efficacy data included results of decoquinate against
artificial infection of single or mixed species of the target
pathogens in floor pen/battery trial and field situations.
The trial designs, treatment group sizes, ages of chickens used,
experimental conditions, administration of test and reference
products, sample collection and analysis of data were generally
appropriate for establishing the efficacy and margin of safety of
the test product under normal use conditions.
In nine dose determination studies in broiler chickens,
decoquinate at inclusions greater than 30 ppm was more effective
than at inclusions equal to or lower than15 ppm in controlling each
of the target Eimeria spp.
In five dose confirmation studies in broiler chickens,
decoquinate administered in-feed at 20, 30 and 40 ppm post
challenge was effective in arresting sporozoites of Eimeria,
compared to salinomycin and robenidine. Each dose was effective,
with 30 ppm and 40 ppm being most effective against all of the
target species. Some sporozoites of E. maxima were able to progress
to gametocytes before degenerating.
One floor pen and one battery trial assessed decoquinate at 30
ppm when fed to broiler chickens prior to the birds being
inoculated with mixed species of Eimeria. The coccidiostat was
effective against each Eimeria species, compared to untreated,
uninfected controls and untreated, infected controls.
In a confirmatory field study conducted in Australia in broiler
chickens, DECCOX-medicated feed at 30 ppm was effective against an
artificial infection of Australian species of Eimeria, compared
with untreated controls and positive controls.
Results of three microbiological studies of E. tenella and E.
necatrix in chickens suggested the potential of Eimeria exists to
develop resistance to decoquinate under practical field usage in
intensive animal production. Resistance was evidence after
relatively few passages.
Claims of efficacy against Eimeria tenella, E. necatrix, E.
acervulina, E. mivati, E. maxima and E. brunetti are supported when
DECCOX is administered in-feed at 30 ppm and fed continuously from
day old to slaughter to broiler chickens.
8.2 Evaluation of target animal safety data
Three target animal safety studies were conducted in which male
and female broilers were fed decoquinate continuously at inclusions
of 15, 30, 40, 90, 150 and 300 ppm for several weeks. Except for
males in the 30 ppm group, weight gains and feed efficiency were
greater than controls. No adverse effects were recognised
pathologically in organs that could be attributed to treatment.
Abnormal clinical signs were not evident. At 400 ppm, feed and
water intakes were not affected adversely, although the chickens
consumed more feed and water. Haematological findings in treated
groups were not different to controls, but biochemical findings
were different.
In two other studies, decoquinate showed no detrimental effects
when fed continuously at 40 ppm for a longer period to male and
female broiler breeders.
In acute oral toxicity studies, broiler chickens showed no gross
visible lesions at necropsy after being administered doses of 1
g/kg or 5 g/kg body weight decoquinate once by gavage. Chicks
showed no effects over 7 days to one oral treatment of 0.11, 1.1 or
11 g decoquinate/kg bw. In contrast, 3200 ppm decoquinate in-feed
depressed growth of chickens for 31 days within 7 days of the birds
being fed in a sub-acute study. Males had lower white blood cell
counts and heterophil count increased in females.
In chronic toxicity studies, there were no macroscopic or
histopathologic drug effect caused by inclusions of 75, 80, 160,
750, 800 and 1600 ppm decoquinate fed to chickens for up to 180
days. Differences in heterophils and white cell counts were not
considered significant. In another chronic toxicity study, day old
chicks tolerated decoquinate fed at 10,000 and 100,000 ppm in
rations for 28 days. The main observed effect was a decrease in
testes weights in chicks in the 100,000 ppm treatment group. At 64
days, treated chicks had lowered haematological values for PCV, WBC
and lymphocyte counts, and pale, clay-like faeces.
8.3 Conclusions
Under normal use conditions, DECCOX is effective in preventing
and controlling Eimeria infections in broiler chickens. It should
be noted that decoquinate does not provide a therapeutic level of
control of all endogenous stages of the life cycle of Eimeria.
Tolerance/safety studies have shown that broiler chickens tolerated
the product at very high inclusions and that the product has a very
wide margin of safety in the event of over-dosage.
9 Labelling requirements
Signal heading:
CAUTION
KEEP OUT OF REACH OF CHILDREN
FOR ANIMAL TREATMENT ONLY
Product name:
DECCOX®
Active constituent:
Decoquinate 60g/kg
Statement of claims:
For the prevention and control of coccidiosis in broiler
chickens – caused by
Eimeria tenella, E. necatrix, E. acervuline, E. mivati, E.
maxima and E. brunetti.
Net contents:
25 kg
Directions for Use Heading:
DIRECTIONS FOR USE:
Restraints:
DO NOT USE in laying hens
Precaution
USE with caution in feeds containing bentonite.
DECCOX should not be mixed with rations containing bentonite.
Bentonite is a type of clay that is used as a compacting and
dispersing agent in some feeds. This is not because bentonite
interferes with the activity of DECCOX in the feed, but because it
interferes with the assay method. Simply put, samples of feed
containing bentonite and DECCOX would not assay properly.
Therefore, feed formulations containing bentonite should be
avoided.
Dosage & administration:
Mixing Directions: Must be thoroughly mixed with other feed
ingredients at the following rates:
Prevention and control of coccidiosis
Broiler chickens
Thoroughly mix 0.5kg/tonne of Deccox in each tonne of complete
ration to provide 30mg decoquinate per kilo and feed continuously
as the only source of feed from day-old to slaughter.
General directions:
General advice is not to use the same in-feed anticoccidial for
extended periods, to rotate among different classes of ionophores
and to rest each product periodically. Use of a synthetic or
chemical product once a year is recommended to clean up field
strains.
Withholding Periods
MEAT: Zero (0) days
EGGS: DO NOT USE in chickens which are producing or may in the
future produce eggs or egg products which may be used or processed
for human consumption
Safety Directions:
May irritate the eyes. Avoid contact with eyes. Wash hands after
use.
Environmental Protection Statement:
Protection of Wildlife, Fish and Crustaceans and the
Environment
DO NOT contaminate or wetlands or watercourses with this product
or used containers.
First Aid:
If poisoning occurs, contact a doctor or Poisons Information
Centre. Phone Australia 131126.
Disposal:
Shake and empty contents into medicated feed. Do not dispose of
undiluted chemicals on-site. If not recycling, break, crush or
puncture and deliver empty packaging to an approved waste
management facility. Empty bag and left-over product should not be
burnt.
Storage:
Store below 25°C (Air Conditioning).
The following is for APVMA use only:
APVMA approval no.
66670/54134
Abbreviations
ac
active constituent
ADI
Acceptable Daily Intake (for humans)
ARfD
Acute Reference Dose
bw
bodyweight
d
day
DT50
Time taken for 50% of the compound to dissipate
EC50
concentration at which 50% of the test population are
immobilised
ErC50
concentration at which the rate of growth of 50% of the test
population is impacted
ESI
Export Slaughter Interval
Eq
equivalent
Fo
original parent generation
g
gram
GLP
Good Laboratory Practice
hr
hour
HPLC
High Pressure Liquid Chromatography or High Performance Liquid
Chromatography
in vitro
outside the living body and in an artificial environment
in vivo
inside the living body of a plant or animal
kg
kilogram
Koc
Organic carbon partitioning coefficient
kt
kilotonne
L
Litre
LC50
concentration that kills 50% of the test population of
organisms
LD50
dosage of chemical that kills 50% of the test population of
organisms
LOD
Limit of Detection – level at which residues can be detected
LOEL
Lowest Observable Effect Level
LOQ
Limit of Quantitation – level at which residues can be
quantified
M/F
male/female
mg
milligram
mL
millilitre
MRL
Maximum Residue Limit
NEDI
National Estimated Daily Intake
NESTI
National Estimated Short Term Intake
NOEC/NOEL
No Observable Effect Concentration Level
PCV
pack cell volume
PEC
predicted environmental concentration
PNEC
predicted no effect concentration
PPE
Personal Protective Equipment
ppm
parts per million
RBC
Red Blood Cell Count
TGAC
Technical grade active constituent
TLC
thin layer chromatography
TRR
Total Radioactive Residues
µg
microgram
WBC
White Blood Cell Count
WHP
Withholding Period
Glossary
Active constituent
The substance that is primarily responsible for the effect
produced by a chemical product
Acute
Having rapid onset and of short duration.
Carcinogenicity
The ability to cause cancer
Chronic
Of long duration
Codex MRL
Internationally published standard maximum residue limit
Efficacy
Production of the desired effect
Formulation
A combination of both active and inactive constituents to form
the end use product
Genotoxicity
The ability to damage genetic material
Leaching
Removal of a compound by use of a solvent
Metabolism
The chemical processes that maintain living organisms
Toxicokinetics
The study of the movement of toxins through the body
Toxicology
The study of the nature and effects of poisons
References
National Occupational Health and Safety Commission 2004, NOHSC
Approved Criteria for Classifying Hazardous Substances.
� A full definition of ‘confidential commercial information’ is
contained in the Agvet Code.
� This section is previously known as the Pharmaceutical
Chemistry Section.
� Agricultural commodity statistics 2014: ABARES
� Australian Chicken Meat Federation (ACMF) Inc, as published in
October 2011: � HYPERLINK
"http://www.chicken.org.au/industryprofile/page.php?id=5.3_Exports"
�www.chicken.org.au/industryprofile/page.php?id=5.3_Exports�
